CD8 co-receptor bound to MHC class I (CD8-MHCI)

The CD8 co-receptor bound to MHC class I is a critical molecular assembly in the adaptive immune system, essential for the recognition and elimination of infected or malignant cells by cytotoxic T lymphocytes (CTLs) (nih.gov, 2024). CD8, typically a heterodimer of alpha and beta chains, functions as a co-receptor by binding to the invariant alpha 3 domain of the Major Histocompatibility Complex (MHC) class I molecule (frontiersin.org, 2024). This interaction occurs simultaneously with the binding of the T-cell receptor (TCR) to the peptide-MHC (pMHC) complex, forming a stable tripartite structure that enhances the sensitivity of antigen detection (nih.gov, 2024). By recruiting the intracellular kinase Lck to the TCR-CD3 complex, CD8 facilitates the rapid initiation of signaling pathways necessary for T-cell proliferation, cytokine production, and cytolytic activity (oup.com, 2024). In the context of disease, tumors often downregulate MHC class I to evade CD8+ T-cell-mediated destruction, while dysregulation of this interaction is implicated in autoimmune pathologies such as polymyositis (nih.gov, 2020; nih.gov, 2025). Modern immunotherapies, including soluble TCRs like tebentafusp and engineered TCR-T cells, are designed to exploit or bypass this interaction to restore effective anti-tumor immunity (clinmedjournals.org, 2019).

Other names

CD8-MHC class I complexCD8-pMHCI complexCD8-HLA class I complexCD8-MHC I interaction

The CD8 co-receptor binds to the non-polymorphic alpha 3 domain of the MHC class I molecule, stabilizing the interaction between the T-cell receptor (TCR) and the peptide-MHC (pMHC) complex. This binding facilitates the recruitment of the Src family tyrosine kinase Lck to the TCR-CD3 complex, which phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) on the CD3 chains, thereby initiating the downstream signaling cascade required for T-cell activation and effector function.